Non-Hodgkin?s lymphomas occur with increased frequency (3-6%) in HIV-infected individuals. These AIDS-associated lymphomas (AAL) exhibit characteristics that distinguish them from lymphomas in the general population. A proposed model for the pathogenesis of AAL includes the following 1) Tumorigenesis is multistep; 2) Tumors occur in long-term survivors; 3) Tumors are of clonal B-cell origin; 4) HIV acts early and is an indirect effector; 5) tumor cells are infected with EBV; and 6) Specific genetic lesions occur in tumor cells. Many aspects of this process remain to be tested in an animal model system. Since 1984, over 1200 necropsies on SIV-infected rhesus and cynomolgus monkeys have been performed at the TRPRC. Lymphoid malignancies were detected in a proportion of SIV-infected animals. These SAIDS-associated lymphomas (SAL) have been studied by histology, immunohistochemistry, in situ hybridization, Southern blotting, and PCR to determine the extent to which their pathologic al features recapitulate a working model for the pathogenesis of AAL. The results show that lymphomas occur in SIV-infected rhesus macaques at an incidence similar to that of AAL, and that the incidence of SAL in cynomolgus macaques is 8-fold higher. Analysis of SAL from both species of macaques demonstrated significant similarity to the hallmark pathobiological features of AAL. The tumors occur in long-term survivors of SAIDS, exhibit extranodal anatomic distribution, represent clonal expansions of B-cell origin, lack SIV in tumor cells, and are infected with RhLCV (a herpesvirus closely related to EBV). These findings indicate that the HIV-infected human and the SIV-infected macaque share a common pathobiology and mechanism of lymphomagenesis. FUNDING NIH-NCI RO1 CA74731 (Levy, PI) PUBLICATIONS Baskin GB, A Habis, M Murphey-Corb, LS Levy. SIV-associated lymphoma in rhesus monkeys a model for AIDS-associated lymphoma. Proceedings of the 16th Annual Symposium on Nonhuman Primate Models for AIDS, Atlanta, GA, (Abstract # 41), 1998.